An active avoidance behavioral paradigm for use in a mild closed head model of traumatic brain injury in mice

Background: A mild traumatic brain injury (TBI) occurs to millions of people each year. Translational approaches to understanding the pathogenesis of neurological diseases and the testing of the effectiveness of interventions typically require cognitive function assays in rodents. New methods: Our goal was to validate the active avoidance task using the GEMINI avoidance system in a mouse model of mild closed head injury (CHI). Results: We found that shock intensity had only a marginal effect on the test. We found that sex was an important biological variable, as female mice learned the task better than male mice. We demonstrate that a single mild CHI in mice caused deficits in the task at four weeks post-injury. Comparison with existing methods: Active avoidance is a classical conditioning test in which mice must pair the presence of a conditioned stimulus with moving between two chambers to avoid an electric shock. External conditions (i.e., apparatus), as well as inherent differences in the mice, which may not be directly linked to the model of the disease (i.e., sensory differences), can affect the reproducibility of a behavioral assay. Before our study, there was a lack of standard operating procedures and validated methods for the active avoidance behavior for phenotyping mouse models of injury and disease. Conclusion: We offer a method for validating the active avoidance test, and a standard operating procedure, which will be useful in other models of neurological injury and disease.